A Crystal Form of a Fluorine-substituted Pyridopyrazole Compound and a Preparation Method Thereof

Abstract

A crystal form of a fluorine-substituted pyridopyrazole compound and a preparation method thereof. Further provided is an application of the compound and the crystal form thereof in preparation of a drug for treating a related disease.

1 . A crystal form A of a compound in Formula (I), wherein its X-ray powder diffractometer (XRPD) spectrum has characteristic diffraction peaks at the following 2θ angles: 17.7805±0.2000°, 22.0193±0.2000°, 27.4192±0.2000°, 
       
         
           
           
               
               
           
         
       
     
     
         2 . The crystal form A according to  claim 1 , wherein, its XRPD spectrum has characteristic diffraction peaks at the following 2θ angles: 15.0010±0.2000°, 17.0603±0.2000°, 17.7805±0.2000°, 22.0193±0.2000°, 23.5013±0.2000°, 27.4192±0.2000°;
 and/or, the crystal form A according to claim  2 , wherein, its XRPD spectrum has characteristic diffraction peaks at the following 2θ angles: 8.1387±0.2000°, 15.0010±0.2000°, 16.1591±0.2000°, 17.0603±0.2000°, 17.7805±0.2000°, 22.0193±0.2000°, 23.5013±0.2000°, 27.4192±0.2000°, 
 and/or, the crystal form A according to claim  3 , wherein, its XRPD spectrum has characteristic diffraction peaks at the following 2θ angles: 8.1387±0.2000°, 13.6809±0.2000°, 15.0010±0.2000°, 16.1591±0.2000°, 17.0603±0.2000°, 17.7805±0.2000°, 22.0193±0.2000°, 23.5013±0.2000°, 24.0218±0.2000°, 27.4192±0.2000°; 
 and/or, the crystal form A according to claim  4 , wherein, its XRPD spectrum has characteristic diffraction peaks at the following 2θ angles: 8.1387°, 9.8194°, 13.6809°, 15.0010°, 16.1591°, 17.0603°, 17.7805°, 18.4386°, 19.5400°, 21.3193°, 22.0193°, 23.1597°, 23.5013°, 24.0218°, 26.1791°, 26.6006°, 27.1199°, 27.4192°, 29.1595°, 29.7190°, 30.8417°, 31.2196°, 32.2992°, 32.9612°, 33.7773°, 34.3779°, 35.1796°, 37.1408°; 
 and/or, the crystal form A according to claim  5 , wherein, its XRPD spectrum is basically shown in  FIG.  1     
 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The crystal form A according to  claim 1 , wherein, its differential scanning calorimeter (DSC) curve has a starting point of an endothermic peak at 107.89±3.00° C., and has a peak of an exothermic peak at 147.76±3.00° C. 
     
     
         8 . The crystal than A according to  claim 7 , wherein, its DSC spectrum is shown in  FIG.  2   . 
     
     
         9 . The crystal form A according to  claim 1 , wherein, the weight loss of its thermal gravimetric analyzer (TGA) curve reaches 0.06% at 200.0±3° C. 
     
     
         10 . The crystal form A according to  claim 9 , wherein, its TGA spectrum is shown in  FIG.  3   . 
     
     
         11 . The crystal form A according to  claim 1 , wherein, its single crystal X-ray diffraction data are as follows: monoclinic crystal system, space group C2, crystal cell parameters a=22.0128(6)Å, b=12.7542(3)Å, c=16.0152(4)Å, α=γ90°, β=90.4900(10)°, volume V=4496.2(2)Å 3 , absolute configuration parameter Flack value of 0.04(3). 
     
     
         12 . A preparation method for a crystal form A of a compound in Formula (1), comprising:
 1) adding the compound in Formula (I) to a solvent to form solution;   2) adding an anti-solvent to the solution, stirring at a certain temperature for a period of time, and filtering, drying a filter cake under a reduced pressure;   wherein,   the solvent is an ester solvent, an ether solvent, or an alcohol solvent;   the anti-solvent is n-heptane, n-hexane, or water;   the stirring temperature is 0-40° C.;   the stirring time is 12-48 hours.   
     
     
         13 . An application of the crystal form A according to  claim 1  in preparation of a drug for treating a disease related to BTK. 
     
     
         14 . The application according to  claim 13 , wherein, the disease related to BTK is hematoma or autoimmune disease. 
     
     
         15 . The crystal form A according to  claim 2 , wherein, its differential scanning calorimeter (DSC) curve has a starting point of an endothermic peak at 107.89±3.00° C., and has a peak of an exothermic peak at 147.76±3.00° C. 
     
     
         16 . The crystal form A according to  claim 15 , wherein, its DSC spectrum is shown in  FIG.  2   . 
     
     
         17 . The crystal form A according to  claim 2 , wherein, the weight loss of its thermal gravimetric analyzer (TGA) curve reaches 0.06% at 200.0±3° C. 
     
     
         18 . The crystal form A according to  claim 17 , wherein, its TGA spectrum is shown in  FIG.  3   . 
     
     
         19 . An application of the crystal form A according to  claim 2  in preparation of a drug for treating a disease related to BTK. 
     
     
         20 . An application of the crystal form A according to  claim 11  in preparation of a drug for treating a disease related to BTK. 
     
     
         21 . An application of the crystal form A according to  claim 7  in preparation of a drug for treating a disease related to BTK. 
     
     
         22 . An application of the crystal form A according to  claim 15  in preparation of a drug for treating a disease related to BTK. 
     
     
         23 . An application of the crystal form A according to  claim 9  in preparation of a drug for treating a disease related to BTK. 
     
     
         24 . An application of the crystal form A according to  claim 17  in preparation of a drug for treating a disease related to BTK.